JOURNAL OF THE AMERICAN CHEMICAL SOCIETY MAY 9,
VOI.IIME
N ~ J M R.E iR
1914
[CONTRIBUTION FROM THE CHEMISTRY IARORATDRY, S A T I O N A I . INSTITUTE OF HI.:ALTH,
l'.
s. P U R I A C HEALTHSRRVICE I
The Acetolysis of Trimethylene-D-sol. 2,4-1VIethylene-D-sorl>itoland 1,3 :2,4-~~ethylene-D-sorb~tol BY A. T.NESS, RAYMOND M. HANNAND C. S. HUDSON Recently' we have shown that the limited aceto- yield a diacetyl-di-(acetoxymethy1)-monomethyllysis of the trimethylene-D-mannitolof Schulz and ene-D-sorbitol; it was found that the acetolysis of Tollens yields a compound to which has been ten- trimethylene-D-sorbitol by an ice-cold 1% sulfuric tatively assigned the structure l,G-diacetyl-3,i-di- acid acetylating solution for five minutes gave a (acetoxymethyl) - 2,5 - methylene - D - mannitol. 51% yield of a crystalline reaction product (m. p. +29.8' in chloroform), the comThis structure seems highly probable since the sa- 111-112'; [ ~ ] M D ponification of the acetolysis product yields a position of which agreed with that of the expected .2,5-methylene-~-mannitol,a fact which we take substance. The compound was sapoaified by the to indicate that the acetal linkages of trimethyl- method of Kunza with the consumption of four ene - D -mannitol which are formed through molecular equivalents of sodium hydroxide, and secondary hydroxyl groups are relatively more the saponification product proved to be a crystalstable to acetolysis than those formed through line monomethylene-D-sorbitol (m. p. 163-164' ; primary hydroxyl groups. The acetolysis ap- [ Y ] ~ O D -9.8' in water). Oxidation of this product parently proceeds with rapid rupture of the acetal w t h sodium periodate (and other glycol-splitting linkages a t positions one and six and the 3,4-di- reagents) reduced one molecular equivalent of (hydroxymethyl) - 2,5 methylene - D - mannitol the oxidant and proved that only a single glycol which is assumed to be formed is immediately grouping is present in the monomethylene-D-soracetylated to produce 1,6-diacetyl-3,4-di-(acetoxy- bitol. At this stage of the study the experimental methyl)-2,5-methy~ene-~-mannito~. In view of results in the case of trimethylene-D-sorbitol are the unusual nature of the acetolysis reaction, and thus closely parallel with those previously reparticularly since the acetolysis product and the ported for the isomeric trimethylene-D-mannitol. 2,5-methylene-~-mannitol derived from it contain However, the periodate oxidation of the 2,5the rare CsOZdioxepane ring as an integral part of methylene-D-mannitol proceeded without the protheir structures, it seemed of interest to study the duction of acid or formaldehyde, thereby confirmAcetolysis of the known trimethylene-D-sorbitd.* ing the structure assigned to it, whereas 0.86 of a In the course of preparation of a supply of this molecular equivalent of formaldehyde was isomaterial we isolated from the mother liquor a di- lated as the crystalline dimethone derivative from methylene-D-sorbitol, a new substance, which the oxidized solution of the monomethylene-Dmelted a t 174-175' and rotated [a]% -29.6' in sorbitol. One hydroxyl group of the glycol groupwater, and the investigation was extended to in- ing of methylene-D-sorbitol is therefore primary clude the acetolysis arid proof of structure of this in chwacter and the structure Of the acetal canriot be 2,s but is limited to that of 2,4 or 3,5diacetal. Considerixig first the trinirthyleIie-u-sorbitol,it methylene-D-sorbitol. A choice between these is obvious that its acetal linkages must be formed two possibilities could be readily made; the oxithrough four secondary and two primary hydroxyl dation of 2,4-methylene-~-sorbitol(111) with groups. From our previous experience it was an- glycol-splitting reagents would yield 2,4-methylticipated that upon limited acetolysis it would ene-L-xylose, which upon reduction would be converted to 2,4-methylene-xylito1 (IV)of mem con(1) Ness. Hann and Hudson, THISJOURNAL, (16. 2216 (1848).
-
(2) Srhillz and Tallena, A m , SED, 23 (1SQfi).
(a)
Kiinz. Tnra JnmNAr.. 48, 1982 (1926).
A. T. NESS, RAYMOND iM. HANNAND C . S. HUDSON
666
r
Vol. 66
solution, which had changed in rotation [CY]''D from an original I value of -9.8' (calcuL-0-CH CHI -0-LH CHz I oxidation lated as 2,4-methylene-~HA-OJ I HC-0-J sorbitol) to - 17.6' (calI culated as 2'4-rnethyleneHCOH pentose), was found to I H2COH be strongly reducing to 0-1) (1) Fehling solution; re1,3:2,4-Dimethylene1,3:2,4 :5,6-Trimethylenemoval of the acids and o-sorbitol n-sorbitol the solvent left the colorI less sirupy oxidation j. product, which did not AcOCHZ AcOCHs crystallize; this sirup was I I reduced in aqueous solu" T O 1 tion a t 100' for six hours AcOCHnOCH CHI AcOCHtOCH CHz with Raney nickel and I I I hydrogen under a presH C - 0 2 H&-O---J sure of 133 atmospheres. I I HCOCHzOAc HCOAc The crystalline reduction I I product (m. p. 108HXOAC HICOAC logo), which did not re(11) (VI11 duce Fehling solution 1,6-Diacetyl-3,5di1,5,6-Triacetyland had the composition 3-acetoxymethyl(acetoxymethyl)-2,42,4-rnethylene-o-sorhi to1 methylene-Do-sorbi to1 of a monomethylenepentitol, was optically inactive in aqueous soluHsCOH tion, from which fact the I conclusion was drawn HC-OCHO I 1 I that it is the mero 2,4HOCH CHd methylenexylitol rather than the 2,4-methyleneD-arabitol. Exact proof of this conclusion was obtained through the preparation of authentic 2,4methylene-xylitol from xylitol, as described in the accompanying artide4; the substances from the two sources are identical. The production of 2,4-methylenexylitol (IV) from the monome thylenesorbitol limits the structure of the latter to 2,4-methyleneD-sorbitol (111) and this conclusion makes i t probable that trimethyleneD-sorbitol is 1,3:2,4:5,6trimethylene - D - sorbitol (I) (since a 1,5- or 1,6figuration and therefore optically inactive; on the acetal ring is highly improbable) and that the other hand, the oxidation of 3,5-methylene-~- intermediate product obtained by the acetolysis sorbitol would produce 2,4-methylene-~-arabh1ose,of trimethylene-D-sorbitol is 1,6-diacetyl-3,5-di(11). reducible to 2,4-methylene-~-arabitol, the formula (acetoxymethyl)-2,4-methylene-~-sorbitol Considering next the dimethylene-D-sorbitol of of which represents an optically-active system. To decide the question, methylene-D-sorbitol was m. p. 174-175' and rotation [ c Y ] ~ O D -29.6' in oxidized by aqueous per-iodic acid ; the oxidation water, it was found that upon oxidation in dilute was complete in fifteen minutes and the oxidized '41 Iiann. Ness and Hudson, TEISJOURSAL. 66, 670 (184.1).
"F-"1
HnC
J.
"T-I
.1
-
-O--CH2 HC- 0
--, I Periodate
May, 1944
ACETOLYSIS OF SOMEMETHYLENE-D-SORBITOLS
667
aqueous solution with sodium periodate, only (VI) is obtained from the reaction mixture emslightly more than one molecular equivalent of ployed for the preparation of trimethylene-Doxidant was consumed, and the yield of crystal- sorbitol, suggests that it is a precursor of the latline formal-dimethone from the oxidized solution ter compound; support for this inference was atcorrespondedto 0.98 nolecular equivalent of form- tained when it was found that upon treatment aldehyde. In further experiments, the other oxi- with formaldehyde and hydrochloric acid the dation product, which proved to be an aldehydo- crystalline diacetal was converted in 85% yield dimethylene-pentose monohydrate, crystallized into the triacetal; this experimental result also spontaneously from the oxidation mixture; the offersfurther support for the previously expressed compound, which rotated [aI2O~-33.9' in water view that the triacetal is 1,3:2,4:5,6trimethyleneand melted a t 175-180' after previous sintering D-sorbitol (I). Apparently the rare CSOsdioxeat 150') was converted upon sublimation to the pane ring that is present in 1,3:2,5:4,6-trimethylanhydrous dimethylene-pentose, which melted ene-D-mannitol is absent from the structure of the a t 189-192' and rotated -38.7' in aqueous solu- isomeric trimethylene-D-sorbitol. The two subtion; it was characterized as the crystalline oxime, stances are structural rather than stereoisomers, a substance which melted with decomposition a t and in view of this result it seems obvious that 227-228' and showed the unusually high rotations the methylene derivatives of the other hexitols [CY]~OD -272' in pyridine and -215' in water. should be investigated similarly. The structure of the aldehydo-dimethylene-penExperimental tose is limited by reason of the genesis of the substance from dimethylene-D-sorbitol to aldehydoI. Substances Derived from Trimethylene--sorbitol 2,3,4,5-dimethylene-~-xylose or aldehydo-2,3,4,51,3:2,4:5,6Trimethylenb~eorbitol (I) and 1,3:2,4-Didimethylene-D-arabinose. Conclusive proof that methylene-lo-sorbitol (VI) from lo-Sorbitol, Formaldehyde it is the former compound was obtained in the and Concentrated Hydrochloric Acid-A solation of 200 g. D-sorbitol in a mixture of 300 cc. of 37% aqueous formalfollowing manner: upon reduction with hydrogen of dehyde and 200 cc. of concentrated hydrochloric acid was and Raney nickel it is converted to a crystalline heated at 50' for four days; after cooling the reaction mixdimethylene-pentitol melting at 217-219' and ture t o 5" for several hours the trimethylene-&sorbitol rotating [:]20D -25.3' in aqueous solution; this which had crystallized was sepiuated by filtration and the was again heated at 60"for several days; no further pentitol diacetal is transformed by limited ace- filtrate deposition of triacetal occurred and the solution *as emtolysis to the 1,5-diacetyl-3-acetoxymethyl-2,4- ployed for the isolation of 1,3:2,4-dimethylene-~-sorbitol methylene-xylitol (meso) (V) that is obtained by as described in the following paragraph. The trimethylenethe limited acetolysis of the 2,4 :3,5-dimethylene- D-sorbitol, which was obtained in a yield of 162 g. (SS%), recrystallized from 20 parts of water or 50% alcohol D,L-xylitol which is described in the accompany- was as long rods which melted at 212-216' and rotated [ a ] * " D ing comm~nication.~This result is definitive -30.8' in chloroform (c, l.Z).6 Schulz and Tol1ens;f proof that the optically active pentitol diacetal record a melting point of 206" and rotations [a]*%-30.3 ( [~]ZOD- 25.3') is 2,4: 3,5-dimethylene-~-xylitol (c, 2.58)and -29.3' (c, 4.578)in chloroform. The mother liquor of the triacetal preparation was (IX) ; it follows that the aldehydo-dimethylene- neutralized with sodium carbonate, the sodium chloride pentose and the dimethylene-ssorbitol from which which precipitated was separated by filtration, and the it is derived must be aldehydo-2,4:3,5-dimethylene- filtrate was concentrated in vacuo to dryness; the dry resiL-xylose (VIII) and 1,3:2,4-dhethylene-~-sorbi- due was extracted with two 200-&. portions of hot absolute alcohol and the extract upon cooling deposited 35 g. to1 (VI), respectively. of fine needles (m. p. 150-168') which after several reThe formation of an optically inactive acetoly- crystallizations from 40 parts of acetone yielded 19.0 g. sis product ( 1,5-diacetyl-3-acetoxymethyl-2,4-of pure 1,3:2,4-dimethylene-~-sorbitol melting a t 174methylene-xylitol, meso stwcture (V)) from the 175' and rotating [a]% -29.6' in water (c, 1.47). The yield was 8% based on the D-sorbitol used or 26% based optically active 2,4 :3,5-dimethylene-~-xylitol (IX) on the D-sorbitol which did not form trimethylene-Dis additional evidence supporting our previously sorbitol. The diacetal is soluble in cold water, dioxane, expressed view that the limited acetolysis of pyridine and acetic acid, in warm methyl and ethyl alcomethylene sugar alcohol acetals takes place in- hols and practically insoluble in ether, carbon tetrachloride itially through a rupture of the acetal linkage a t a and chloroform. Calcd. for CsH~rOrn: C,46.60; H, 6.84. Found: primary hydroxyl group; had the acetal rupture C,Anal. 46.66; H, 6.92. of (IX) occurred a t any other position than car1,bDiacetyl-J,J-di-( acetoxymethyl)-2,4-methylene-~ bon five the acetolysis product would be expected sorbitol (II).-Eighty grams of dried and powdered trit o possess optical rotatory power. methylene-D-sorbitol was added to a rapidly stirred iceConfirmatory evidence for the assigned struc- cold mixture of 175 cc. of acetic anhydride, 75 cc. of glacial acid and 2.5 CC. of concentrated sulfuric acid; ture of 1,3:2,4-dimethylene-~-sorbitol (VI) was acetic solution of the triacetal was rapid and after five minutes also obtained through its acetolysis to form the reaction mixture was poured into 3 liters of vigorously stirred ice water. The acetolysis product crystallized and the expected 1,5,6-triacetyl-3-acetoxymethyl-2,4methylene-D-sorbitol (VII), a compwnd which after two hours the crystalline product was separated by (5) All the crystalline compounds described in the experimental is saponified by sodium methylate with the prowere recrystallized to constant melting point and specific rotaduction of the previously isolated 2,Cmethylene- pait tion; c is the concentration in grams in 100 cc. of solution: the tube D-sorbitol (111). length n o s 4 dm.; all melting points were determined with the stem The fact that 1,3 :2,4-dimethylene-~-srbitolof the calibrated thermometer immened in the rapidly rtirred bath.
A. T. NESS, RAYMOND M . HA"
868
AND
C. S. HUDSON
Vol. 66
-2.6" at the expiration of fifteen and sixty minutes, four, filtration, washed with cold water and air dried. The twenty and ninety-two hours, respectively; these changes yield was 80 g. (52%). The compoupd was recrystallized from 12 parts of alcohol as long needles which melted at in rotatory power are presumably due to the change of the 111-112' and rotated [CY]% +29.8" in chloroform ( c . aldehydo form of the methylene-pentose to the equilibrium 1.20). It is soluble in acetone, chloroform, benzene, acetic mixture of its a and ~3cyclic forms (probably a- and &2,4acid and pyridine and practically insoluhle in water, ether methylene-L-xylopyranose) . sodium Periodate Oxidation of 2,4-Methyfene-~and cold methyl and ethyl alcohols. Anal. Calcd. for CtrHtaO~p:C, 48.34; H, 6.20; saponi- sorbitol.-The oxidation of 1.0045 g. of 2,4-methylene-~fication, 0.1452 g. substance requires 13.75 cc. 0 . 1 9Ka0I-l sorbitol with 15 cc. (1.65 molecular equivalents) of 0.570 (4 saponifiable groups). Found: C, 48.41; H, 6.10; .If sodium periodate was conducted by the same procedure saponification, 0.1452 g. substance consumed 13.75 CY, employed in the per-iodic acid oxidation. The analytical results showed that 1.01, 1.03 and 1.02 molecular equiva0 . 1 ;V NaOH. 2,4-Methylene-~-sorbitol {IIX).-A solution of IO g. of lents of oxidant had been consumed a t the end of twenty, forty and sixty minutes, respectively, and the formal1,f: - diacetyl - 3,5 - di - (acetoxymethyl) . 2 , 4 - methylenewhorbitol i r i 100 cc. of chloroform was cooled in an ice- dimethone recovered was 86% of that expected for the IJath a i d 10 cc. of 0.2 N sodium methylate solution was production of one rnolecular equivalent of formaldehyde, added; upon standing a t 5' for eighteen hours, 4.6 g. The specific rotation [a]'OD of the oxidized solution reI quantitative) of 2,4-methylene-~-sorbitol crystallized mained constant ar 18.4" for three hours and thereafte: showed values of -15.3, -11.9, -4.1. -3.6 and -2.6 from the reaction mixture. The acetal was recrystallized from 50 parts of alcohol in the form of fine needles which a t the expiration of nineteen, forty-three, one hundred nielted a t 163-164" and rotated [ a ] 2 %-9.8" in aqueous eighty-seven, two hundred twelve and two hundred eightysolution (c, 1.30). It is readily soluble in water, hot methyl three hours, respectively, the reduced rate of mutarotation and ethyl alcohols and practically insoluble in chloroform, in this case being probably due to the lower hydrogen-ion concentration. acetone and ether. 2,4-Methyleneqlitol (IV)from 2,CMethylene-D-sorAnal. Calcd. for GHlrOa: C, 43.29; H, 7.27. Found. bitol (III).-A solution of 5.0 g. of 2,4-methylene-~-sorbitol C, 43.27; H, 7.25. in 5Occ. of water wascooled to5Oand50cc. (1.20molecular 1,3,5,6-Tetwcetyl-2,4-rnethylene-~-sorbitol.-A solu- equivalents) of 0.616 ill aqueous per-iodic acid was added; tion of 2.0 g. of 2,4-methylene-~-sorbitol in a mixture of the reaction mixture was allowed to stand at 25' for 15 cc. of acetic anhydride and 10 cc. of pyridine was eighteen hours, cold saturated barium hydroxide solution allowed to stand for forty-eight hours at 25" and then was added in slight excess, the precipitated barium iodate poured into ice-water ; the precipitated tetraacetyl deriva- and periodate were separated by filtration and the filtrate tive, which is soluble in chloroform, acetone, acetic acid, was concentrated in vacuo t o a dry sirup in the presence of pyridine and benzene and practically insoluble in water barium carbonate. The sirup was extiacted with 50 cc. of and cold methyl and ethyl alcohols, was recrystallized from warm water and the extract, which was reducing to Feh10 parts of alcohol as prismatic needles melting a t 150- ling solution, was transferred to a bomb and agitated at 1-51' aiid rotating [a]*%-1.5" in chloroform ir, 1.40). 100' for six hours with Raney nickel and hydrogen under a The yield was 3.6 g. (94%). pressure of 133 atmospheres. The catalyst was separated .4nal. Calcd. for C15H22010: C.49.72; H, 6.12: CHICO, by filtration and the filtrate, upon concentration in vucuo, -17.5. Found: C, 49.80; H, 6.03; CHsCO, 47.3. deposited a crystalline residue (4.2 g. ; quantitative) Lead Tetraacetate Oxidation of 2,4-Methylene-~- which was recrystallized from 5 parts of alcohol and sorbitol.-To a solution of 0.1018 g. of 2,4-methylene-~- yielded 2.9 g. of the 2,4-methylene-xylitol (m. p. 108-109 ") sorbitol in 15 cc. of glacial acetic acid, 30 cc. (3.32 mole- which is described in the accompanying comm~nication.~ cular equivalents) of 0.0581 M lead tetraacetate glacial The isolation and identification of this methylene-pentitol acetic acid solution was added and the volume was ad- is a definitive proof that the methylene-D-sorbitol from iusted to 50 cc. with glacial acetic acid, all operations being which it is derived is 2,4-methylene-~-sorbitol. conducted a t 25". Analysis of 5 cc. subsamples a t one, .4nal. Calcd. for CGHI~CS:: C, 43.90; H, 7.37. Found: three and nineteen hours indicated that 0.67, 1.00 and 1.04 C, 43.83; 13, 7.35. molecular equivalents, respectively, of oxidant had been 11. Substances Derived from 1,3:2,4-Dhethylene-~consumed. The analytical data indicate that 2,4-methylsorbitol me-D-sorbitol contains a single glycol grouping as a por5,6-Diacetyl-1,3:2,4-dimethylene-~-sorbitol. -A solution tion of its structure. Per-iodic Acid Oxidation of 2,4-Methylene-~-sorbitol.-- of 1.0 g. of the previously described 1,3:2,4-dimethylene.i solution of 1.0036 g. of 2,4methylene-~-sorbitolin 25 D-sorbitol in a mixture of 10 cc. of acetic anhydride and 10 cc. of water w a s cooled to 5" and 15 cc. (1.79 molecular cc. of pyridine was allowed to stand a t 25' for seventy-two equivalents) of 0.616 ;If per-iodic acid was added; the hours and then poured into 600 cc. of ice water; the solu.ohtion was allowed to warm to 20" and the volume was tion was extracted with chloroform and the washed and adjusted to 50 cc. with water. Analysis of 5 cc. aliquots at dried extract was concentrated in vacuo to a crystalline twenty, forty and sixty minutes showed that 1.04 mo- residue which upon crystallization from 10 parts of alcohol lecular equivalents of oxidant had been consumed and no formed plates melting a t 136136' and rotating [a]% - 12.8" in chloroform (c, 1.08). The compound is soluble further oxidation was noted after twenty and two hundred sixty hours. After titration, the first three aliquots were in acetone, benzene, chloroform, acetic acid and ethyl combined and poured into 200 cc. of 0.4% dimethone acetate and insoluble in water. The yield was 1.2 g. (S6%). solution; the precipitate of formal-dimethone (m. p. 189Anal. Calcd. for CltHl~Os:C, 49.65; H, 6.25; CHaCO. 190") which deposited on keeping the mixture at 5" for 29.7. Found: C, 49.60; H, 6.27; CHaCO, 29.8. eighteen hours, weighed 0.387 g. and represented 857, of 5,6-Dibenzoyl-l,3:2,4-dimethylene-~-sorbitol.-The dithat expected from the production of one molecular benzoate was obtained by the action of benzoyl chloride equivalent of formaldehyde as an oxidation product. The on 1.3: 2,4-dimethylene-~-sorbitol pyridine solution. results of the oxidation show that the glycol grouping of The yield was 2.1 g. (quantitative).in The compound de2,4-methylene-~-sorborbitolmust contain a primary alcohol posited from its solution in 10 parts of alcohol form group since the anslytical lindings agree with the reaction of needles melting at 134-135" an! rotating in the -54.8" course C6HoOpCHOH.CHsOH 4- HI04 = C~HSOUCHO in chloroform (c, 1.08); it is soluble in pyridine, acetic acid, + HCHO HzO 4-HIOi. Although the analyses mentioned above &ow that the oxidahon was complete within acetone and ethyl acetate and insoluble in water. Anel. Calcd. for C Z Z H Z ~ O C,~63.76; : H, 5.35; CeHaCO, twenty minutes under the experimental conditions, the speciiie rotation [a]% of the solution (calculated on its 50.7. Found: C, 63.61; H, 5.37; CsH6C0, 50.8. Sodium Periodate Oxidation of 1,3:2,4-Dimethylene-~presumed content of methylene-pentose) showed values of -17.6, -14.5. -6.2, -3.1' and a constant value of sorbitol (VI)"--A solution of 1.0619 g. of 1,3:2,4-dimethyl-
-
+
May, 1944
ACETOLYSIS OF SOMEMETHYLENE-D-SORBITOLS
689
crystallized in eue-u-sorbitol in 20 cc. of water was cooled to 5' and 25 cc. alcohol; the 2,4:3,5-dimethylene-~-xylitol (2.10 molecular equivalents) of 0.432 M aqueous sodium needles which melted at 217-219" and rotated [a]% -25.3" in aqueous solution (c, 1.09). The compound is periodate was added; the mixture was allowed to warm to 25' and the volume was adjusted to 50 cc. with water. one component of the crystalline 2,4:3,5-dimethylene~ ~ o ~is described in the accompanying comAnalysis of 5-cc. aliquots at the expiration of twenty D , L - x Y ~which minutes, two and twenty hours indicated that 1.00, 1.03 munication.' A more detailed comparison of these two and 1.04 molecular equivalents, respectively, of sodium substances is made in that article. periodate had been reduced. After titration, the first two Anal. Calcd. for C~H1206: C, 47.72; H, 6.87. Found: aliquots were poured into 200 cc. of 0.4% dimethone C, 47.64; H , 6.83. solution and the mixture; upon preservation a t 5' for l-Acetyl-2,4:3,5-dimethylene-~-xylitol. -This compound forty-eight hours, deposited 0.2124 g. of formal-dimethone, was prepared by the acetylation of 2,4:3,5-dimethylene-~which' is 98% of that expected if one molecular equivalent xylitol (1.0 9.) in pyridine solution (10 cc.) by acetic anof formaldehyde was produced as a product of the oxida- hydride (10 Cc.). The yield was 1.0 g. (83%). I t was retion. These analyses prove that the dimethylene-D- crystallized from 12 parts of alcohol in the form of rods sorbitol contains a terminal glycol grouping as a part of which melted at 153-154" and rotated [a]% +2.8' in its structure. They indicate that the dimethylene-acetal chloroform (c, 0.96); it is soluble in acetone, ethyl acetate, was oxidized with the formation of formaldehyde and an carbon tetrachloride and acetic acid and practically inaldehydo-dimethylene-pentose. Support for this assump- soluble in water. A microscopic optical crystallographic tion was obtained when it was noted that the specific examination by Mr. George L. Keenan, of the Food and rotation, [ a l Z o D -37.1 (calculated as aldehydo-dimethyl- Drug Administration, Federal Security Agency, showed me-pentose), of the oxidized solution did not change in that in parallel polarized light (crossed nicols) the extincvalue even on standing for one-hundred twenty hours, an tion was parallel and the elongation negative, the refracobservation which would be expected only in the absence tive indices being ne = 1.484, ng = 1.504 and n, = 1.524, of a ring form of the sugar (compare the rotation changes all *0.002. of the oxidized solution of 2,4-methylene-~-sorbitolwhich Anal. Calcd. for COHUO~:C, 49.54; H, 6.47; CHaCO, presumably contains 2,4-methylene-~-xylose,a sugar ca- 19.7. Found: C, 49.58; H,6.48; CH'CO, 19.7. pable of existing in a and j3 cyclic forms). 1,5-Diacetyl-J-acetoqmethy1-2,4-methylene-xylitol (V) aldehydo-2,4:3,5-Dimethylene-~-xylose Monohydrate suspension of from 1,3:2,4-Dimethylene-~-sorbitol(-).-A solution of from 2,4:3,CDimethylene~-xylitol(=).-A 1.0 g. of 2,4:3,5-dimethylene-~-xylitol in a mixture of 7.0 $5.0g. of 1,3:2,4-dimethylene-~-sorbitol in 50 cc. of water cc. of acetic anhydride and 3.0 cc. of glacial acetic acid was was cooled to 5" and 75 cc. (1.3 molecular equivalents) of ' and 10 cc. of an acetylating solution (prepared 0.432 M aqueous sodium periodate was added. Within cooled to 0 thirty minutes small needles started to deposit in the as described for the acetolysis of trimethylene-D-sorbitol) solution and after the mixtufe had been allowed to stand cooled to 0' was added; the mixture was agitated until in the refrigerator for eighteen hours they were separated solution of the alcohol diacetal was complete (ten minutes) and after a further five minutes it was poured into 400 cc. by filtration. The yield was 2.6 g. (565;). The product was recrystallized from 10 parts of water as needles which of ice water. The solution was nearly neutralized by the rotated [a]% -33.9' in aqueous solution (c, 0.!2) and addition of 35 g. of sodium bicarbonate and extracted with melted at 175-180' after prior sintering at 150 The three 50 cc. portions of chloroform; the washed and dried substance is soluble in warm water and acetic acid and extract was concentrated to a crystalline residue (1.4 g.; practically insoluble in warm methyl and ethyl alcohols, 78%; m.p. 13&145') which was recrystallized from 30 parts of hot water and yielded 0.8 g. of pure 1,5-diacetyl-3; chloroform, acetone and dioxane. Anal. Calcd. for CrHloO~H20: C, 43.75; H, 6.30. acetoxymethyl-2,4-methylene-xylitolmelting at 139-140 and devoid of rotation in aqueous solution (c, 0.92). A Found: C, 43.78; H, 6.34. mixed melting point with the compound prepared by the aZdekydo-2,4:3,5-Dimethylene-~-xylose(VIII).-A sam- acetolysis of 2,4 :3,5dhnethylene-~,~-xylitol~ also showed mono- 139-140", a result which was anticipated since the acetople of 0.5 g. of aldehydo-2,4:3,5-dimethylene-~-x~lose hydrate was sublimed in a vacuum at 140-145 ; the subo lysis of either the optically active (IX)or racemic form of limate of fine needles showed a melting point of 189-192 the diacetal according to the acetolysis mechanism which and a specific rotation [a]?"D -38.7" in water (c, 0.44); has been proposed should yield the meso 1,5-diacety1-3no mutarotation was observed in twenty-four hours. acetoxymethyl-2,4-methylene-xylitol(V). Anal. Calcd. for CTHIOOS:C, 48.27; H, 5.79. Found: 1,5,6-Triacetyl-3-aceto~ethyl-2,4-methylene-~eorC, 48.02; H, 5.92. bitol (VII) from 1,3:2,4-Dimethylene-~-sorbitol(VI).-A Oxime of aldehydo-2,4:3,5-Dimethylene-~-xylose.-A solution of 1.0 g. of 1,3:2,4dimethylene-~-sorbitol in 5 cc. mixture of 1.0 g. aldehydo-2,4:3,5-dimethylene-~-xyloseof an ice-cold 1% sulfuric acid acetylating mixture was monohydrate, 1.0 g. of hydroxylamine hydrochloride, 1.0 allowed to stand at 0' for five minutes and then poured g. of fused sodium acetate, 25 cc. of methyl alcohol and 5 into 200 cc. of ice-water; the flocculent precipitate which cc. of water was refluxed for twenty minutes. Upon stand- formed (0.6 g.; 32%) was separated by filtration and reing at 5 " for seireral days the solution deposited 0.8 g. crystallized from 7 parts of alcohol. The compound, which (80%) of product, which upon recrystallization from 100 crystallized as fine needles, melted at 94-95" and rotated [a]% +11.0' in chloroform (c, 1.04); it is readily soluble parts of alcohol yidded small lath-like crystals which melted a t 227-228' and rotated [a]% -272' in pyridine in acetone, ethyl acetate, acetic acid, pyridine and warm (c, 0.50). Because the magnitude of this rotation is un- methyl and ethyl alcohols and practically insoluble in usual for this type of compound, its rotation was also water. determined in aq!eous solution (c, 0.31); it was found to Anal. Calcd. for CisHe&: C, 48.98; H, 6.16; saponibe [a]% -215.0 . The oxime is soluble in pyridine, hot fication, 0.1139 g. substancerequires 11.61 cc. 0.1 N NaOH water and hot alcohol and practically insoluble in cold alco- (4 saponifiable groups). Found: C, 49.05; H, 6.21; hol, acetone and chloroform. saponification, 0.1139 g. substance consumed 11.58 cc. 0.1 Anal. Calcd. for C7HllOsN: C, 44.44; H, Fj.86; N, N NaOH. 7.40. Found: C, 44.43; H , 5.86; N, 7.45. 2,4-Methylene-~sorbitol (m) from 1,5,6-Triacetyl-32,4:3,5-Dimethylene-~-.ylitol (E) from aldehydo-2,4: acetoxymethyl-2,4-methylene-~-sorbitol (VII).-To an ice3,5-Dimethylene-~-ryloseMonohydrate.-A solution of cold solution of 2.0 g. of 1,5,6-triacetyl-3-acetoxymethyl6.0 g. of 2,4:3,5-dimethylene-~-xylose monohydrate in 2,4-methylene-~-sorbitol in 30 CC. of chloroform, 5 cc. of 200 cc. of water was agitated in a bomb at 25' for eighteen 0.2 N sodium methylate solution was added and the reachours with Raney nickel and hydrogen at a pressure of 133 tion mixture was allowed to stand a t 5' for seventy-two atmospheres; the catalyst was separated by filtration and hours; the precipitate which had deposited was separated the filtrate was concentrated in vacuo to a crystalline m a s by iiltration and ,recrystallized from 20 parts of alcohol; (5.0 g.; 91%) which was recrystalked from M) parts of the needles which formed showed a melting point of 163-
.
NESS
AND
C'. S. HUDSON
i'(11. tiii
10.1' and a specific rotation [a]% -9.7' in aqueous solu1,X : 3,4-dimethylene-~-sorbitol since upoii pei-ic, tion, these data being in agreement with those previously date oxidation it yields an aldehydo-2,4:3,5-di found for the 2,4-methylene-~-sorbitol obtained by the saponification of 1,6-diacetyl-3,5-di-(acetoxymethyl)-2,4-methylene-L-xylose which is successively convertec f I 1,5-diacetyl-$ methylene-D-sorbitol (11). A mixed melting point deter- to 2 ,:3,5-dimethylene-L-xylitol, mination with 2 , I-methylene-n-sorbitol from this source acetoxymethyl-2,4-methylene-xylitol and 2,4 showed no depression. me thylene-xylitol by known reactions.
1,3:2,4:5,6-Trimethylene-~-sorbitol(I) from 1,3:2,4Dimethylene-D-sorbitol (VI).--A solution of 1.0 g. of 1,3: 2,4-dimethylene-~-sorbitol (VI) in a mixture of 1.(I cc, of concentrated hydrochloric acid and 1.0 cc. of :F(:i aqueous formaldehyde was warmed to 50"; within thirty minutes crystallization of needles was noted and after forty-eight hours the mixture was cooled to j0,the needles were separated by filtration, washed with ice-cold .50(:, alcohol, and dried. The yield was 0.90 g. (85%). 'l'hc product, after recrystallization from 20 parts of 5 0 ' , alcohol, showed a melting point of 210-214" aiid a niixtd iiieltitig point determination with authentic trimethylentiwwrhilol showed no depits:jlWl.
The fact that the limited acetolysis of 2,4:3,5diniethylene-L-xylitol forms a compound of meso structure rather than one possessing optical at.tivity is cited as evidence supporting the prc2viously proposed acetolysis mechanism based oi I the hypothesis that the acetal linkages of nitthvleiie acetals which ate formed through primary :tlcoholic groups are more easily ruptured thal, those formed through secondary alcoholic groups ; this experimental corroboration allows assignmerit of the structures of 1,6-diacetyl-3,3-diSummary (acetoxymethvl)-2,4-niethylene-D-sorbitol and 1,'The condensation of n-sorbitoi with formalde- 5,B- triacetyl-3- (acetoxymet hyl) - 2,4 - methylene-~,hyde under the influence of concentrated hydro- sorbitol, respectively, to the acetolysis products chloric acid yields, in addition to the known tri- of trimethylerie-~-s:)rbitoland 1,3:2,4-diinethvlmethylene-D-sorbitol of Schulz and Tollens, a ene-D-sorbitol. ITI view of the press-t experimental results, new crystalline &methylene-D-sorbitol: The h i i ted acetolysis of the known trimethylene-D-sorbi- and particularly the coiiclusive establishment of to1 yields a diacetyl-di-(acetoxyethyl)-methyl- the presence of the 2,4-acetal linkage, it seenis ene-hexitol, which upon saponification is trans- highly probable that the trimethylene-D-surbitol formed into a crystalline methylene-D-sorbitol o f Schulz and Tollens is J , 3 :2,4: 5,6-trirnethyleiiethat can be only 2,4-methylene-~-sorbitolsince u-sorbitol, the rare e602 dioxepane ring that is it is converted by periodate oxidation and subse- present in 1,s:2,5:4,6-trimethylene-~-niannitolbe quent reduction to 2,4-rnethylene-xylitolof proved iiig absent from the structure of the isomeric. triniethlilerie-D-sorbitol. structure. 'fhe new dimethylene.-D-sorbi~(jlCUI: be only HETHESUA, > ~ A R Y I , A N U RECEIVED JANUARY 21, 183-1
u. s. PUBLIC HEALTHSERVICh I 2,4:3,5-Dimethylene-~,~-xylitol and 2,4-Methylene-xylitol
[('OYTRIBUTIOV FROM THE CHEMISTRY L A B O R A T O R Y , h - A T 1 0 V . 4 ~ INSTITUTE OF HEALTH,
BY RAYMOND 11.1 K.~NN. A 'I' NESSAND C. S. HUDSON In the course of the study of the acetolysis oi trimethylene-D-sorbitol that is described i i i the accompanying article' there was obtained by degradative reactions a monomethylene-peiititol (in. p. 108-109°) the structure and configuratioii of which needed to be established. I n configuration it is limited to a monomethylene derivative uf xylitol or D-arabitol by reason of its origin. In aqueous solution no optical rotation was detected, which indichted the probability that the compound is a moriomethylene-xylitol of meso structure since all structures for a monomethylene-Darabitol represent optically active systems. The direct identification of its constituent pentitol through acid hydrolysis seemed of little attraction because of the experimental difficulties that are often encountered in attempts to hydrolyze methylene cyclic acetals. Accordingly, it was sought to produce the substance by condensing formaldehyde with xylitol, a procedure which, if 1) X e s s , Hann and H u d s o n , Tal3 J o u R - n ~ ,66. 665 (1944)
successful, would establish the identity of its colistituent pentitol and might also lead to a less laborious method for obtaining i t , 'There appears to be no recorded combination of formaldehyde with xylitol, although dibeiizylidelle2 and di-isopropylidene xylitols3 are knowti. Ai crystalline dimethylene-xylitol (m. p. 20 1202') was obtained in 91% yield by the reaction of xylitol with 37% aqueous formaldehyde slid concentrated hydrochloric acid for two hours at 50". One of the methylene groups in this dimethylene-xylitol is readily removable, as will be described, and the resulting nioiiomethyleriexylitol proved to be identical with the nioiioinethylene-pentitol (m. p. 108-109°) which was obtained from trimethylene-D-sorbitol. This nioiiumethylene-xylitol does not react with sodiuiti periodate and thus i t contains no a-glycol group; (2) (a) I,. d e Bruyn a n d van Ekenstein, Rcc. !raw. chrm., 18, 151 (1899);(bj Wolfrom'and Kohn, THIS JOURNAL, 6.4, 1739 (1942). (31 ( a ] Tipson and Cretcher, J. 07s. Chcm., 8, 95 (19431; (b) H a u n . Ness und H u d s o n , T H I S J U U R X A L . 66, 73 (1944).
